Bacteria are ubiquitous, and are found in previously considered uninhabitable environments. They are common and diverse ecologically, and find unusual and common niches for survival. They are present throughout the environment, and are present in soil, dust, water, and on virtually all natural surfaces. Many are normal and beneficial bacterial strains, which provide a synergistic relationship with hosts. Others are not so beneficial, or cause problems along with benefits under specific conditions.
Pathogenic bacteria can cause infectious diseases or significant symptoms in humans, in other animals, and also in plants. Some bacteria can only affect particular hosts; others cause trouble in a number of hosts, depending on host specificity of the bacteria. Others may be innocuous or dormant in certain circumstances, and can emerge as problems in other contexts or situations. Diseases caused by bacteria, whether alone or in combinations, are almost as diverse as the bacteria themselves and include food poisoning, tooth decay, anthrax, general infectious diseases, and even certain forms of cancer. These clinical issues are typically the subject of the field of clinical microbiology.
Bacteria are natural targets of certain viruses, e.g., bacteriophage, or phage. Phages have evolved on their natural hosts, and have a very fast rate of replication and evolution. Phage can capitalize on the least vulnerability presented by the physiology or biology of their hosts. As such, appropriate harnessing of phage structure, physiology, and principles should be useful to minimize or control bacteriological caused problems.
Certain bacteria are normally innocuous, but become pathogenic upon presentation of the appropriate opportunity, or become problematic upon introduction to an abnormal site or situation. Moreover, certain bacterial combinations evolve together and may operate synergistically to complement functions lacking in individual members of a colony. However, many assorted mechanisms exist, e.g., in a multicellular organism, to handle different amounts of bacteriological challenge, and the complete eradication of the bacterial cultures is often not necessary. In many cases, incomplete eradication of the bacterial population will decrease the effects of infection to allow the system to resolve problems by alternative mechanisms, e.g., the immune system.
Statistically, infectious diseases are a major medical problem. See, e.g., Watstein and Jovanovic (2003) Statistical Handbook on Infectious Diseases Greenwood, ISBN: 1573563757. In the U.S., some 40-70K deaths result from bloodstream nosocomial (hospital derived) infections each year.
In particular, antibiotics have revolutionized clinical medicine over the last half century. Since the original discovery of antibiotic phenomena, the mechanism of action and development of this class of remarkable therapeutic entities has made enormous progress. See, e.g., Therrien and Levesque (2000) FEMS Microbiol. Rev. 24:251-62; Durgess (1999) Chest 115(3 Suppl):19S-23S; Medeiros (1997) Clin. Infect. Dis. 24(Suppl 1):S19-45; Jones (1996) Am. J. Med. 100(6A):3S-12S; Ford and Hait (1993) Cytotechnology 12:171-212; and Liu (1992) Compr. Ther. 18:35-42. Antibiotics had about $32B worldwide sales in 2002.
The widespread appearance of antibiotic-resistant bacteria has emphasized the vulnerability of current antimicrobial treatments to bacterial adaptation. See, e.g., Wise (2007) “An overview of the Specialist Advisory Committee on Antimicrobial Resistance (SACAR)” J. Antimicrob. Chemother. 60 Suppl 1:i5-7. PMID: 17656382; Finch (2007) “Innovation—drugs and diagnostics” J. Antimicrob. Chemother. 60 Suppl 1:i79-82, PMID: 17656390; Walsh (1992) Antibiotics: Actions, Origins, Resistance Amer. Soc. Microbiol., ISBN: 1555812546; Cunha (1992) Antibiotic Essentials Physicians Press, ISBN: 1890114413; Amyes (2003) Magic Bullets, Lost Horizons: The Rise and Fall of Antibiotics Taylor & Francis, ISBN: 0415272033; Axelsen (2001) Essentials of Antimicrobial Pharmacology: A Guide to Fundamentals for Practice Humana Press, ISBN: 0896038424; and Mainous and Pomeroy (eds. 2001) Management of Antimicrobials in Infectious Diseases: Impact of Antibiotic Resistance Humana Press, ISBN: 0896038211.
In addition, mechanisms of antibiotic resistance develop under minimally selective conditions (e.g., at low concentration of antibiotic), and these mechanisms are often transferred between hosts. Thus, mechanisms evolve in different organisms, and often are introduced into new hosts, where these same mechanisms are further refined and optimized. Often combinations of mechanisms are generated, genetically linked together, and are transferred together among bacterial hosts. These combinations often result in genetic clustering of DNA segments encoding linked multiple drug resistance markers
Thus, improved methods for decreasing prevalence of resistance encoding plasmids, growth, or survival or for limiting bacterial virulence or pathogenicity will find great utility. This utility may be applicable to environmental, local, topical, or particularly in vivo colonization. The present invention addresses these and other significant problems.